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Biochim Biophys Acta Mol Cell Biol Lipids. 2017 Mar;1862(3):358-368. doi: 10.1016/j.bbalip.2016.12.009. Epub 2016 Dec 23.

Critical role of the peroxisomal protein PEX16 in white adipocyte development and lipid homeostasis.

Author information

1
Institute of Biochemistry, Graz University of Technology, Austria.
2
Institute of Molecular Biology and Biochemistry, Medical University of Graz, Austria.
3
Institute of Cell Biology, Histology and Embryology/Center for Medical Research, Medical University of Graz, Austria.
4
Institute of Molecular Biosciences, University of Graz, Austria.
5
Institute of Molecular Biosciences, University of Graz, Austria; Omics-Center, BioTechMed, Graz, Austria.
6
Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria.
7
Institute of Biochemistry, Graz University of Technology, Austria. Electronic address: juliane.bogner-strauss@tugraz.at.

Abstract

The importance of peroxisomes for adipocyte function is poorly understood. Herein, we provide insights into the critical role of peroxin 16 (PEX16)-mediated peroxisome biogenesis in adipocyte development and lipid metabolism. Pex16 is highly expressed in adipose tissues and upregulated during adipogenesis of murine and human cells. We demonstrate that Pex16 is a target gene of the adipogenesis "master-regulator" PPARγ. Stable silencing of Pex16 in 3T3-L1 cells strongly reduced the number of peroxisomes while mitochondrial number was unaffected. Concomitantly, peroxisomal fatty acid (FA) oxidation was reduced, thereby causing accumulation of long- and very long-chain (polyunsaturated) FAs and reduction of odd-chain FAs. Further, Pex16-silencing decreased cellular oxygen consumption and increased FA release. Additionally, silencing of Pex16 impaired adipocyte differentiation, lipogenic and adipogenic marker gene expression, and cellular triglyceride stores. Addition of PPARγ agonist rosiglitazone and peroxisome-related lipid species to Pex16-silenced 3T3-L1 cells rescued adipogenesis. These data provide evidence that PEX16 is required for peroxisome biogenesis and highlights the relevance of peroxisomes for adipogenesis and adipocyte lipid metabolism.

KEYWORDS:

Adipogenesis; Lipid homeostasis; PEX16; PPARγ; Peroxisome

PMID:
28017862
DOI:
10.1016/j.bbalip.2016.12.009
[Indexed for MEDLINE]
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